Magnetic resonance (“MR”) imaging has become a well-accepted and commonly-used technique for studying a wide range of physiologic processes. This technology is useful in connection with disease diagnosis and prognosis, and in the broader study of biological systems. Indeed, many hospitals and medical facilities have MR imaging equipment on-site, and routinely make use of it to aid in the diagnoses and monitoring of an array of diseases and physiologic conditions. Contrast agents or reporter molecules are used in connection with MR imaging, and a wide range of products is commercially available to image various systems. Along these lines, there remains a strong need in the art for improved reporter molecules for use in connection with MR imaging for a wide range of diseases and physiologic conditions.
It is remarkable that NMR has contributed so much to our understanding of the brain and other organs using only part-per-million polarizations. That MRI is possible at all is due to slight variations in the density or relaxation times of the highly concentrated (˜80 M) water protons. The in vivo study of metabolism with 1H, 13C or 15N NMR by previous methods has been possible only with little or no spatial localization and prolonged signal averaging that largely precludes the study of dynamics and is severely limited by cost.
The Boltzmann distribution leads to low signal to nose ration (SNR) in NMR spectroscopy. This has been accommodated in the application of NMR spectroscopy to analytical chemistry by using concentrated samples and signal averaging. However, in biology, NMR spectroscopy has yet to reach its full potential for the simple season of time limitation associated with high number of transients required to obtain sufficient SNR under the biological constraints of low concentration, physiological temperature, and high dielectric losses. Nowhere is this more relevant than in the brain, where neurochemical events occur on the spatial and temporal scale of electrical neurotransmission (second to milliseconds).